CDK6 protects epithelial ovarian cancer from platinum-induced death via FOXO3 regulation.

ABSTRACT: Epithelial ovarian cancer (EOC) is an infrequent but highly lethal disease, almost invariably treated with platinum-based therapies. Improving the response to platinum represents a great challenge, since it could significantly impact on patient survival. Here, we report that silencing or pharmacological inhibition of CDK6 increases EOC cell sensitivity to platinum. We observed that, upon platinum treatment, CDK6 phosphorylated and stabilized the transcription factor FOXO3, eventually inducing ATR transcription. Blockage of this pathway resulted in EOC cell death, due to altered DNA damage response accompanied by increased apoptosis. These observations were recapitulated in EOC cell lines in vitro, in xenografts in vivo, and in primary tumor cells derived from platinum-treated

SUBMITTER: Dall'Acqua A 

PROVIDER: S-EPMC5623833 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature